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Category: life extension – Page 448

The DNA Damage Response in Aging

DNA damage, which results in genomic instability, is one of the primary hallmarks of aging. Today, we want to highlight an recent open access review that explores the DNA damage response during aging.

The role of DNA damage

Some researchers have long suggested that damage to our DNA is a major reason why we age and a strong determinant of species longevity; indeed, many-long lived species have extremely stable genomes, such as bristlecone pines, which have lifespans of over 5000 years.

Tryptophan as a Therapeutic Target for Inflammaging

A new open access paper takes a look at tryptophan and the role that it plays in the dysfunction of the immune system in the context of the age-related changes that occur in the microbiome [1].

The microbiome

The gut microbiome is a complex ecosystem of bacteria, archaea, eukarya, and viruses that live inside of us, some beneficial and some harmful, the balance of which keeps us alive. Four microbial phyla, Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria, make up 98% of the total population of the intestinal microbiome.

Alzheimer’s drug candidates reverse broader aging, study shows

In mouse models of Alzheimer’s disease, the investigational drug candidates known as CMS121 and J147 improve memory and slow the degeneration of brain cells. Now, Salk researchers have shown how these compounds can also slow aging in healthy older mice, blocking the damage to brain cells that normally occurs during aging and restoring the levels of specific molecules to those seen in younger brains.

The research, published last month in the journal eLife, suggests that the drug candidates may be useful for treating a broader array of conditions and points out a new pathway that links normal aging to Alzheimer’s disease.

“This study further validated these two compounds not only as Alzheimer’s drug candidates but also as potentially more widely useful for their anti-aging effects,” says Pamela Maher, a senior staff scientist at Salk and a co-corresponding author of the new paper.

Nanotech Suggests To Have Found A Way To Combat Age Related Diseases

NaNotics, in another breakthrough, is promising a new kind of medication, and suggests to have found a way to combat age related diseases; boldly going where no nanotech has gone before.

Lou Hawthorne of NaNotics, LLC opened his presentation at a recent longevity investor event using a clip from Star Trek that shows captain Kirk being giving a shot that restores him to his younger years.

“It’s tempting to assume it’s a drug, but what if the content of that syringe was something new?” NaNotics’ CEO Hawthorne asked. “NaNots are a new class of medicine. They are engineered to do just one thing and that’s the holy grail of medicine design, because most drugs do two things: something you want them to do, and something you don’t. In other words, side effects.”

Gut Microbes Support Neurogenesis and Longevity Hormone Production

The relationship between health and the microorganisms living in the gut has increasingly reached the spotlight in the last few years, and a new study led by researchers at Nanyang Technological University, Singapore (NTU Singapore) sheds more light on the gut microbiome and how it can influence aging.

The gut microbiome

The gut microbiome is a complex ecosystem that includes a varied community of bacteria, archaea, eukarya, and viruses that inhabit our guts. The four bacterial phyla of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria comprise 98% of the intestinal microbiome.

Deficiency in the DNA repair protein ERCC1 triggers a link between senescence and apoptosis in human fibroblasts and mouse skin

ERCC1 (excision repair cross complementing‐group 1) is a mammalian endonuclease that incises the damaged strand of DNA during nucleotide excision repair and interstrand cross‐link repair. Ercc1−/Δ mice, carrying one null and one hypomorphic Ercc1 allele, have been widely used to study aging due to accelerated aging phenotypes in numerous organs and their shortened lifespan. Ercc1−/Δ mice display combined features of human progeroid and cancer‐prone syndromes. Although several studies report cellular senescence and apoptosis associated with the premature aging of Ercc1−/Δ mice, the link between these two processes and their physiological relevance in the phenotypes of Ercc1−/Δ mice are incompletely understood. Here, we show that ERCC1 depletion, both in cultured human fibroblasts and the skin of Ercc1−/Δ mice, initially induces cellular senescence and, importantly, increased expression of several SASP (senescence‐associated secretory phenotype) factors. Cellular senescence induced by ERCC1 deficiency was dependent on activity of the p53 tumor‐suppressor protein. In turn, TNFα secreted by senescent cells induced apoptosis, not only in neighboring ERCC1‐deficient nonsenescent cells, but also cell autonomously in the senescent cells themselves. In addition, expression of the stem cell markers p63 and Lgr6 was significantly decreased in Ercc1−/Δ mouse skin, where the apoptotic cells are localized, compared to age‐matched wild‐type skin, possibly due to the apoptosis of stem cells. These data suggest that ERCC1‐depleted cells become susceptible to apoptosis via TNFα secreted from neighboring senescent cells. We speculate that parts of the premature aging phenotypes and shortened health‐ or lifespan may be due to stem cell depletion through apoptosis promoted by senescent cells.

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